The goal of this effort is to develop a novel label-free detection technology for application to protein microarrays. The objective of the Phase I is to build a breadboard prototype to characterize the performance of this new approach and to establish feasibility. The technology is based on a multilayer grating-coupled (MGR) evanescent wave sensing method with the potential to provide highly multiplexed measurements for massively parallel analysis of microarrays with high sensitivity and without the drawbacks and limitations of label-based methods or other label-free methods such as surface plasmon resonance (SPR). This innovation addresses the "detection problem" in proteomics; that is, the difficult and pressing problem of how to accurately measure binding to a protein microarray with high sensitivity and high spatial and temporal resolution. We will build a prototype imaging system and demonstrate multiplexed measurements with prototype microarrays made on disposable sensor chips. Preliminary results provide a solid foundation for the proposed work and indicate a high probability of success. Potential applications range from basic research to drug target discovery to clinical diagnostics. Examples include protein expression profiling; high-throughput ligand fishing, identifying new receptor and natural ligands, immune response characterization, homology studies on protein families, identifying disease markers and others. We believe that the field of drug discovery and development presents one of the largest immediate commercial opportunities for the proposed technology, followed by clinical diagnostics in the longer term. We anticipate that the high-throughput, label-free microarray-based MGR system proposed here will capture a significant segment of these market. PROPOSED COMMERCIAL APPLICATION: Potential applications range from basic research to drug target discovery to clinical diagnostics. Specific examples include protein expression profiling; high-throughput annotation of gene products, defining binding domains, epitopes and interacting molecular motifs, high-throughput ligand fishing, identifying new receptors and natural ligands, immune response characterization, homology studies on protein families, identifying disease markers and others.